Pressure Overload Activates DNA-Damage Response in Cardiac Stromal Cells: A Novel Mechanism Behind Heart Failure With Preserved Ejection Fraction?

ABSTRACT: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome characterized by impaired left ventricular (LV) diastolic function, with normal LV ejection fraction. Aortic valve stenosis can cause an HFpEF-like syndrome by inducing sustained pressure overload (PO) and cardiac remodeling, as cardiomyocyte (CM) hypertrophy and fibrotic matrix deposition. Recently, in vivo studies linked PO maladaptive myocardial changes and DNA damage response (DDR) activation: DDR-persistent activation contributes to mouse CM hypertrophy and inflammation, promoting tissue remodeling, and HF. Despite the wide acknowledgment of the pivotal role of the stromal compartment in the fibrotic response to PO, the possible effects of DDR-persistent activation in cardiac stromal cell (C-MSC)

SUBMITTER: Stadiotti I 

PROVIDER: S-EPMC9259931 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature